The platelet-derived growth factor receptor beta (PDGF-Rβ) is a membrane-spanning tyrosine kinase. The ligand PDGF is composed of combinations of the homologous chains A, B, C and D, combined to either homo- or heterodimers. PDGF-Rβ binds PDGF-BB with high affinity and PDGF-AB with lower affinity. Ligand binding leads to dimerization and trans-phosphorylation of tyrosines in the intracellular kinase domain of the receptors.
PDGF is an important factor for regulating cell proliferation, cellular differentiation, cell growth and development. PDGF-Rβ is implicated in angiogenesis and in early stages of fibrosis. This receptor represents an attractive and potentially valuable target, e.g. for treatment and molecular imaging in for example oncologic and fibrotic diseases.
Antibodies blocking the effect of PDGF-Rβ are in clinical development and the continued provision of agents with a comparable affinity for this receptor remains a matter of substantial interest within the field. Of great interest is also the provision of uses of such molecules in the treatment and diagnosis of disease. It is an object of the invention to provide new PDGF-Rβ-binding agents, which could for example be used for diagnostic, in vitro or in vivo imaging, and therapeutic applications.